Heroin use and treatment admissions for heroin dependence have been increasing steadily over the past several years. Clearly, there is a need for new effective treatments for opioid dependence. Although methadone, levo alpha-acetylmethadol (LAAM), and naltrexone are currently approved for the treatment of opioid dependence, many problems are associated with their use such as patient noncompliance, continued opioid use during treatment, and high relapse rates during withdrawal from treatment. Several possible causes for these problems have been suggested but insufficient research has been conducted to evaluate the effects of these medications on ongoing human behavior in a research laboratory setting. In the proposed research, participants residing in a controlled setting will be given the opportunity to work for heroin and money. These studies will examine the multiplicity of ways in which several current and proposed medications affect heroin consumption, performance, mood, physiological measures, and participants' verbal reports of drug effects. The model thus developed will be used to evaluate potential new medications for opioid abuse as they are developed and before they are put into large multi-center trials. The specific aims of the proposal are to evaluate: l) the effects of the combination tablet containing buprenorphine and naloxone; 2) the time course and efficacy of a depot formulation of naltrexone; 3) the ability of oral naltrexone maintenance to induce supersensitivity to the effects of heroin; and 4) the effects of memantine and dextromethorphan, which are low-affinity N-methyl-D-aspartate receptor antagonists. Several of these medications will also be evaluated in another project as adjunct medications for the treatment of withdrawal during detoxification from heroin. Together, data from these projects should shed light on the effects of these medications on a broad range of heroin's effects, from actual heroin taking to detoxification from heroin.